The respiratory distress syndrome of infancy (RDS) is the largest single cause of death in preterm infants and is thought to be secondary to a lack of pulmonary surfactants. Utilizing recent physiologic, cytologic, and biochemical advances, we have conducted a pilot study which we believe suggests the efficacy of nebulizing two of these surfactants, dipalmitoyl phosphatidyl choline (DPPC) and dipalmitoyl phosphatidyl glycerol (DPPG) to infants with RDS. The objectives of the proposed study are two-fold: 1) to carry out a controlled trial in humans, and 2) to investigate, in an animal model, the relative effects of the addition of other components of the surfactant complex. DPPC is felt to be the major component of the pulmonary surfactant system. However, other phospholipids may have an important role in the pathogenesis of RDS. DPPG, missing in infants with RDS, has the same surface tension lowering characteristics as DPPC and has the potential of enhancing fusion of DPPC to alveolar membranes. Previous attempts utilizing surfactant aerosols may have been unsuccessful because 1) constant distending airway pressure (CDAP) was not used, 2) an emulsion of DPPC rather than DPPC vesicles was used, and 3) DPPC alone without the addition of other possibly essential components of the surfactant complex was used. We sonicated 90% DPPC/10% DPPG to form vesicles which were then nebulized by an ultrasonic nebulizer to RDS infants requiring respirator therapy and CDAP. Improvement, in terms of a decrease in alveolar-arterial O2 gradient, was noted with increasing frequency of administration. We would like to establish the efficacy of this treatment in humans through a controlled trial alternating these surfactants and a placebo. In preterm lambs with RDS, we propose to evaluate the efficacy of replacing other components of the surfactant complex (phosphatidyl serine, phosphatidyl inositol, lysolecithin, cholesterol, and protein) which also have been reported to enhance uptake of DPPC by cultured cells. Various percentages will be added to DPPC, nebulized to lambs in triplicate, and the most promising combination pursued in depth.